A general combined purification and immobilization method to facilitate biocatalytic process development is presented. The support material, EziG™, is based on controlled porosity glass (CPG) or ...polymer-coated versions thereof (HybCPG) and binds protein affinity tags. Biocatalytic reactions in aqueous and organic media with seven enzymes of biocatalytic interest are shown.
Introduction
Intriguingly, autism spectrum disorders (ASD) and symptomatic generalised joint hypermobility (S-GJH) (e.g. hypermobility spectrum disorders and Ehlers Danlos Syndrome) share several ...clinical manifestations including motor difficulties, sensory hypersensitivity and autonomic dysfunction. Moreover, many syndromic forms of ASD manifest a hypermobile phenotype. Despite the increased interest in the area, few systematic studies are available.
Objectives
This large cross-sectional comparative study aimed to examine the association between S-GJH and ASD in adults.
Methods
We assessed GJH by physical examination using the Beighton Scoring System (BSS) and collected data on musculoskeletal symptoms and skin abnormalities amongst 156 adult patients with ASD and 413 adult community controls. A proxy for S-GJH was created by combining a positive BSS with at least one additional musculoskeletal symptom or skin abnormality.
Results
The prevalence of S-GJH was significantly higher amongst patients with ASD than amongst controls (16.7% vs 4.8%, p< .001). A logistic regression model, adjusting for candidate covariates of GJH (age, sex, race), revealed a significant influence of ASD on S-GJH with adjusted odds ratio of 5.4 (95% CI 2.8-10.5, p< .001).
Conclusions
ASD and S-GJH are associated in adults. If recognised, musculoskeletal complications related to S-GJH can be relieved by physiotherapy. Clinicians should be familiar with that symptoms frequently occurring in GJH such as pain, fatigue and orthostatic intolerance may mimic or aggravate psychiatric symptoms (e.g. depression, anxiety). Knowledge about comorbidities may provide clues to underlying aethiopathological factors. Future research to clarify the mechanisms behind this association and to evaluate how comorbid S-GJH affects ASD outcome is warranted.
Disclosure
No significant relationships.
Introduction
There is growing evidence that generalised joint hypermobility (GJH) is associated with several psychiatric conditions. There are no previous studies on adult ADHD.
Objectives
To ...evaluate, in a large Swedish sample, if generalised joint hypermobility and adult ADHD are associated.
Methods
431 adults with ADHD and 417 controls were included. GJH was assessed by the Beighton Score, a physical examination, and the 5PQ, a self-report screening tool. Exploratively, reported musculoskeletal symptoms and abnormal skin manifestations suggestive of symptomatic GJH (e.g. Ehlers-Danlos syndrome), were assessed to differentiate this group from the general GJH group. Logistic regressions determined the influence of an ADHD diagnosis and known covariates (age, sex and ethnicity) on GJH and symptomatic GJH respectively.
Results
ADHD was associated to GJH, as defined by the Beighton Score and the 5PQ, with adjusted odds ratios of 4.65 (CI 95% 3.01-7.18, p<.005) and 1.86 (CI 95% 1.39-2.48, p<.005), respectively. Likewise, ADHD and symptomatic GJH were associated with adjusted odds ratios of 6.94 (CI 95% 4.05-11.89, p<.005) and 2.66 (CI 95% 1.94-3.66, p<.005).
Conclusions
GJH and adult ADHD are associated conditions. Symptomatic GJH, defined as additional symptoms of pain and/or skin manifestations, has a considerably stronger link to adult ADHD than unspecific GJH has. GJH may represent a marker of an underlying systemic disorder with physical manifestations in connective tissue as well as behavioural manifestations including hyperactivity, impulsiveness and inattentiveness. Future studies should investigate if this represents a novel subtype of ADHD and if symptomatic GJH affects the ADHD management.
Disclosure
No significant relationships.
Introduction
Immunological mechanisms may contribute to the causation of mental illness. Autoimmunity is most convincingly shown for anti-NMDA-R encephalitis and Pediatric Acute-Onset ...Neuropsychiatric Syndrome (PANS); disorders that overlap clinically with schizophrenia and OCD. Altered inflammatory cytokine production, glial activation and auto-antibodies have also been associated with schizophrenia and OCD. In these disorders, however, the treatment results with anti-inflammatory or immunomodulating drugs have hitherto been limited and inconsistent. Yet other targets within the immune system may still be effective and new options are warranted for treatment-resistant patients. Rituximab targets B-lymphocytes and is often used in autoimmune disorders such as rheumatoid arthritis, multiple sclerosis and anti-NMDA-R encephalitis.
Objectives
We aimed to investigate whether rituximab is clinically effective, safe and tolerable as add-on therapy in markedly ill, treatment-resistant adult psychiatric patients with schizophrenia or OCD. We also wanted to identify putative mediating mechanisms in treatment responders, such as cytokine changes and functional connectivity (FC).
Methods
In an open pilot study, adults (18-39 years) with treatment-resistant schizophrenia and/or OCD were included. They received an intravenous infusion of rituximab 1000 mg, once at baseline, in addition to their regular psychiatric medication and were followed for 1 year. The main outcome measures were the Positive and Negative Syndrome Scale (PANSS) or Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Clinical Global Impression-Improvement scale (CGI-I) and the Personal and Social Performance scale (PSP). Treatment response was defined as ≥ 40 % decrease in PANSS or ≥ 35 % decrease in Y-BOCS, and much improved according to CGI-I. Resting-state fMRI was applied at baseline and after 5 months. Plasma cytokines were measured at 0, 3 and 5 months. Cognitive tests and the recently developed PsychoNeuroinflammatory Related Signs and Symptoms Inventory (PNISSI) were used to identify and measure symptoms related to neuro-inflammation and cognitive function.
Results
Nineteen patients were treated with rituximab. 3-5 months after treatment, 6/9 patients with schizophrenia and 1/10 with OCD responded. One schizophrenia patient continues with rituximab every 6 months and has reportedly done well for almost 3 years. No severe side effects were reported apart from recurrent abdominal pain in a schizophrenia patient and one case of post-COVID-19 syndrome. Significant changes of FC were detected in responders only and correlated with PSP changes.
Conclusions
Aberrant B-cell activities may contribute to treatment-resistant schizophrenia and be amenable to treatment with rituximab. However, the results of this pilot study need confirmation in placebo-controlled trials.
Disclosure of Interest
None Declared
With the increase of South Asian immigrants in Canada, the relationship between older immigrant Punjabi women's sociocultural relationships and their mental health and well-being needs to be ...understood. Guided by the social determinants of health and intersectional feminist frameworks, five Punjabi women living in Nova Scotia, Canada were interviewed. Three themes were identified: (a) having freedom yet being dependent on families, (b) conflating having a happy family with having good mental health, and (c) needing ways to connect with other older Punjabi women. These findings articulate how Punjabi relationships affect women's views on mental health and well-being.
Background: Detecting and controlling the movements of invasive species, such as insect pests, relies upon rapid and accurate species identification in order to initiate containment procedures by the ...appropriate authorities. Many species in the tussock moth genus Lymantria are significant forestry pests, including the gypsy moth Lymantria dispar L., and consequently have been a focus for the development of molecular diagnostic tools to assist in identifying species and source populations. In this study we expand the taxonomic and geographic coverage of the DNA barcode reference library, and further test the utility of this diagnostic method, both for species/subspecies assignment and for determination of geographic provenance of populations. Methodology/Principal Findings: Cytochrome oxidase I (COI) barcodes were obtained from 518 individuals and 36 species of Lymantria, including sequences assembled and generated from previous studies, vouchered material in public collections, and intercepted specimens obtained from surveillance programs in Canada. A maximum likelihood tree was constructed, revealing high bootstrap support for 90% of species clusters. Bayesian species assignment was also tested, and resulted in correct assignment to species and subspecies in all instances. The performance of barcoding was also compared against the commonly employed NB restriction digest system (also based on COI); while the latter is informative for discriminating gypsy moth subspecies, COI barcode sequences provide greater resolution and generality by encompassing a greater number of haplotypes across all Lymantria species, none shared between species. Conclusions/Significance: This study demonstrates the efficacy of DNA barcodes for diagnosing species of Lymantria and reinforces the view that the approach is an under-utilized resource with substantial potential for biosecurity and surveillance. Biomonitoring agencies currently employing the NB restriction digest system would gather more information by transitioning to the use of DNA barcoding, a change which could be made relatively seamlessly as the same gene region underlies both protocols.
Parents of young children experienced many stressors due to stay-at-home directives in the first wave of the COVID-19 pandemic. Bubbles were implemented by some governments, allowing households to ...connect with another household while minimizing contagion risk, but little is known about their effectiveness. We explored the social support experiences of Canadian mothers living in Nova Scotia during this first wave, focusing on whether they perceived household bubbles to be helpful in reducing parenting stress. In-depth interviews were completed with 18 mothers (aged 21–49) who had at least one child under the age of 12 during the first shutdown. Interviews focused on how they coped during the initial shutdown period, the immediate time after they paired up with another household, and what was happening for them currently (approximately eight to ten months later). Data were analyzed using qualitative description and content analysis through application of topic, descriptive, and analytical coding; memo writing; and matrix analysis. Deciding who to bubble with typically focused on direct support for parents or having playmates for children. Having a bubble arrangement reduced the pressure of the situation, and perceptions of future emergency backup support also reduced anxiety levels. Support from family members who lived far away, however, was still key for some families. Household bubbles play an important role in reducing stress levels during a pandemic through received and perceived support. As the COVID-19 pandemic evolves, policy directives and support interventions need to enhance social support for parents and peer interactions for young children.
The construction of comprehensive reference libraries is essential to foster the development of DNA barcoding as a tool for monitoring biodiversity and detecting invasive species. The looper moths of ...British Columbia (BC), Canada present a challenging case for species discrimination via DNA barcoding due to their considerable diversity and limited taxonomic maturity.
By analyzing specimens held in national and regional natural history collections, we assemble barcode records from representatives of 400 species from BC and surrounding provinces, territories and states. Sequence variation in the barcode region unambiguously discriminates over 93% of these 400 geometrid species. However, a final estimate of resolution success awaits detailed taxonomic analysis of 48 species where patterns of barcode variation suggest cases of cryptic species, unrecognized synonymy as well as young species.
A catalog of these taxa meriting further taxonomic investigation is presented as well as the supplemental information needed to facilitate these investigations.
Mammalian mitochondrial DNA (mtDNA) is replicated by the heterotrimeric Pol γ comprised of a single catalytic subunit, encoded by Polg, and a homodimeric accessory subunit encoded by the Polg2 gene. ...While the catalytic subunit has been shown to be essential for embryo development, genetic data regarding the accessory subunit are lacking in mammalian systems. Here, we describe the generation of heterozygous (Polg2(+/-)) and homozygous (Polg2(-/-)) knockout (KO) mice. Polg2(+/-) mice are haplosufficient and develop normally with no discernable difference in mitochondrial function through 2 years of age. In contrast, the Polg2(-/-) is embryonic lethal at day 8.0-8.5 p.c. with concomitant loss of mtDNA and mtDNA gene products. Electron microscopy shows severe ultra-structural defects and loss of organized cristae in mitochondria of the Polg2(-/-) embryos as well as an increase in lipid accumulation compared with both wild-type (WT) and Polg2(+/-) embryos. Our data indicate that Polg2 function is critical to mammalian embryogenesis and mtDNA replication, and that a single copy of Polg2 is sufficient to sustain life.
Winter mortality is expected to be a key factor determining the ability of mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae), to expand its range in Canada. We ...determined the mortality rate and supercooling points of eggs from the beetle's historic range in southern British Columbia as well as the recently expanded range in north-central Alberta and tested if eggs require an extended period of chilling to reach their maximum cold tolerance. We found no effect of population source or acclimation time on egg cold tolerance. Although 50% of eggs can survive brief exposure to –20.5 °C (LT50), storage at 0.3 °C and –7.5 °C for 59 d resulted in 50% and 100% mortality, respectively. Our results indicate that eggs suffer significant prefreeze mortality and are not well-adapted to overwintering: eggs are unlikely to survive winter throughout much of the beetle's range. Our results provide information that can be used to help model the climatic suitability of mountain pine beetle, including how changes in seasonality associated with new or changing climates may affect winter survival. In addition to lower lethal temperatures, it is critical that the duration of exposure to sublethal cold temperatures are considered in a comprehensive index of cold tolerance and incorporated into survival and population models.
PDF
